Phase III Pancreatic Cancer Trial


Rafael Pharmaceuticals has Initiated a Phase III Trial (AVENGER 500) of CPI-613® (devimistat) in Combination with Modified FOLFIRINOX as First Line Treatment for Patients with Metastatic Pancreatic Cancer

Rafael Pharmaceuticals, Inc. has initiated a Phase III multicenter, open-label, randomized pivotal trial (AVENGER 500) to evaluate the efficacy and safety of its lead compound, CPI-613® (devimistat), in combination with modified FOLFIRINOX (mFFX) as a first-line therapy in patients with metastatic adenocarcinoma of the pancreas.

AVENGER 500 will compare the efficacy and safety of FOLFIRINOX (FFX, control arm) with CPI-613® in combination with mFFX. Patients 18-75 years old of both sexes with metastatic (stage IV) pancreatic adenocarcinoma, not previously treated for metastatic disease and with ECOG performance status of 0 – 1 are eligible for enrollment in this study. The interim analysis of the study is expected to be completed as early as Q2 2020.

An earlier Phase I single-center, open-label, dose-escalation study (CCCWFU 57112, NCT01835041) evaluated the safety, tolerability and efficacy of CPI-613® in combination with mFFX as frontline therapy in patients with metastatic pancreatic cancer. A total of 18 patients were treated at the maximum tolerated dose of 500 mg/m2. Overall, the treatment was well tolerated. No deaths due to adverse events were reported and no patients died while on active treatment. Of the 18 patients given the maximum tolerated dose, 3 had a complete radiographic response, 61% achieved an objective response (OR) with a median overall survival (OS) of 19.9 months and median progression free survival (PFS) of 9.9 months. Given these results, further evaluation of CPI-613® in pancreatic cancer was warranted.

Comments on this Study from Rafael Leadership:

Howard Jonas, Chairman of Rafael Pharmaceuticals: “It is our goal not only to prolong life but ultimately to develop cures for pancreatic cancer and other difficult-to-treat cancers. We have great hope both for the success of this trial and for our follow-on compounds in the years to come. We are optimistic that cancer metabolism drugs will create a new paradigm in oncology treatment.”

Sanjeev Luther, President and Chief Executive Officer of Rafael Pharmaceuticals: “Our motto, ‘To Save A Life Is To Save A Universe,’ reflects our commitment to develop potential treatments for patients with significant unmet clinical needs. Pancreatic cancer is one of the most difficult-to-treat cancers. In the last two decades, the median overall survival following standard frontline therapies in metastatic pancreatic cancer has increased to 11.1 months (FOLFIRINOX). Pancreatic cancer is expected to become the second leading cause of cancer related death after 2020. Our focus is on extending and enhancing the lives of patients with pancreatic and other gastrointestinal cancers. Initiation of the AVENGER 500 trial represents a significant milestone in that direction. Given that the clinical development of CPI-613® started at Wake Forest Baptist Health, we wanted this to be the site to enroll the first patient. We are grateful to all the individuals that have been involved with clinical development of CPI-613®. Given the importance of this trial we have partnered with a reputable contract research organization, Covance, for study execution.”

Philip A. Philip, MD, PhD, FRCP, Principal Investigator of this study: “Pancreatic cancer is the deadliest cancer worldwide with very limited treatment options. The current data on CPI-613® in combination with modified FOLFIRINOX in patients battling pancreatic cancer is immensely promising. I am, therefore, delighted to be involved in this important Phase III trial.”

Timothy Pardee, MD, Ph.D., Chief Medical Officer of Rafael Pharmaceuticals: “I am very excited to see the initiation of this Phase III trial for metastatic pancreatic cancer patients. There is a clear unmet medical need for this population.”

About CPI-613® (devimistat):

CPI-613® (devimistat) is a first-in-class drug, developed based on the Altered Metabolism Directed (AMD) platform. CPI-613® targets altered regulation of metabolic processes specific to cancer cells. It is designed to be highly specific, simultaneously attack multiple targets, minimally toxic and have broad spectrum activity across a wide variety of cancers. CPI-613® is being or has been evaluated in 18 ongoing or completed trials as a single agent, as well as in combination with standard drug therapy for hematological malignancies and solid tumors. To date, over 300 patients have received one or more doses of CPI-613®. In a dose escalation study evaluating the safety, tolerability and efficacy of CPI-613® in pancreatic cancer, CPI-613® in combination with modified FOLFIRINOX exhibited an objective response rate of 61%, median overall survival of 19.9 months and median progression free survival of 9.9 months in 18 patients taking the maximum tolerated dose. In elderly patients with AML, CPI-613® in combination with high dose cytarabine and mitoxantrone exhibited 52% CR+CRi and 12.4 months median overall survival. In T-cell lymphoma, CPI-613® in combination with bendamustine exhibited 75% objective response rate. CPI-613® has been granted orphan drug designation by the U.S. FDA for pancreatic cancer, AML, MDS, peripheral T-cell lymphoma and Burkitt’s lymphoma. The EMA has granted orphan drug designation to CPI-613® for pancreatic cancer and AML.

About Pancreatic Cancer:

Pancreatic cancer is an extremely deadly disease, with more than 95% of patients affected dying of their disease. Although its incidence in the U.S. is relatively low (estimated new cases in 2018 is 55,440)2, pancreatic cancer became the third leading cause of cancer-related deaths in 20163 and is expected to be the second cause of death after 20204 . There are a number of types of pancreatic cancer. The predominant one is adenocarcinoma, which accounts for approximately 95% of exocrine pancreatic cancers.5 Because the disease typically does not present with recognizable/distinctive symptoms in its early stages, when it is diagnosed, it is usually quite advanced and affords limited treatment options. Chemotherapy is the only treatment option for metastatic pancreatic cancer. National Comprehensive Cancer Network (NCCN) treatment guidelines recommend FOLFIRINOX or gemcitabine plus nab-paclitaxel for first-line treatments for patients who are healthy enough to tolerate them and have a support system for a relatively aggressive medical therapy, but efficacy response is limited (FOLFIRINOX6: ORR: 31.6%, OS: 11.1, PFS: 6.4; gemcitabine in combination with nab-paclitaxel7: ORR: 23%, OS: 8.5, PFS: 5.5). However, FOLFIRINOX is regarded as too toxic for use in elderly and poor performance status patients. For patients who wish to pursue cancer-directed therapy but cannot manage such aggressive treatments, gemcitabine alone or alternate choices are recommended. In general, clinical trials are highly recommended for patients with metastatic pancreatic cancer. Another option for patients who cannot tolerate the toxic effects of FOLFIRINOX is to be treated with a modified dosing regimen of FOLFIRINOX, which significantly decreases the adverse side effects (neuropathy, diarrhea, neutropenia) associated with FOLFIRINOX. The 5-year survival rate of patients with metastatic (stage IV) pancreatic cancer is only 1%.8 There is a great medical need for more effective first-line systemic therapies that are less toxic and more effective.

References:

  1. Ecpc.org. (2018). Pancreas. [online] Available at: http://www.ecpc.org/component/tags/tag/52-pancreas [Accessed 7 Dec. 2018].
  2. SEER. (2018). Pancreatic Cancer – Cancer Stat Facts. [online] Available at: https://seer.cancer.gov/statfacts/html/pancreas.html [Accessed 7 Dec. 2018].
  3. Pancan.org. (2018). [online] Available at: https://www.pancan.org/wp-content/uploads/2016/02/2016-GAA-PC-Facts.pdf [Accessed 7 Dec. 2018].
  4. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913-21
  5. Cancer.org. (2018). What Is Pancreatic Cancer?. [online] Available at: https://www.cancer.org/cancer/pancreatic-cancer/about/what-is-pancreatic-cancer.html [Accessed 7 Dec. 2018].
  6. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic cancer. New England Journal of Medicine. 2011;364(19):1817–1825. doi:10.1056/nejmoa1011923.
  7. Hoff DV, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. New England Journal of Medicine. 2013;369:1691-703
  8. Cancer.org. (2018). Pancreatic Cancer Survival Rates, by Stage. [online] Available at: https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html [Accessed 7 Dec. 2018].

Disclosure:
-Tim Pardee MD; Ph.D. was the site principal investigator for early Phase 1/2 clinical trials at Wake Forest Baptist Medical Center.
-Bayard L. Powell, M.D., Section Chief, Hematology & Oncology, Associate Director for Clinical Research, Comprehensive Cancer Center, Professor, Hematology & Oncology, Wake Forest Baptist Medical Center serves as a member of Rafael Pharmaceuticals Medical Advisory Board.
-Boris Pasche MD; Ph.D. Director, Comprehensive Cancer Center and Chairman, Department of Cancer Biology, Wake Forest Baptist Medical Center, serves as a Board Member to Rafael Holdings, Inc. (NYSE American: RFL) which is an investor in Rafael Pharmaceuticals, Inc.

Safe Harbor Statement:
This press release contains forward-looking statements. These statements relate to future events or the company’s future financial performance. In some cases, you can identify forward-looking statements by terminology such as “may”, “will”, “should”, “expect”, “plan”, “anticipate”, “believe”, “estimate”, “predict”, “potential” or “continue”, the negative of such terms, or other comparable terminology. These statements are only predictions. Actual events or results may differ materially from those in the forward-looking statements as a result of various important factors. Although we believe that the expectations reflected in the forward-looking statements are reasonable, such statements should not be regarded as a representation by the company, or any other person, that such forward-looking statements will be achieved. The business and operations of the company are subject to substantial risks which increase the uncertainty inherent in forward-looking statements. We undertake no duty to update any of the forward-looking statements, whether as a result of new information, future events or otherwise. In light of the foregoing, readers are cautioned not to place undue reliance on such forward-looking statements.

Contact

Sanjeev Luther
President & CEO Rafael Pharmaceuticals, Inc.
sanjeev.luther@rafaelpharma.com

Timothy Pardee
Chief Medical Officer, Rafael Pharmaceuticals, Inc.
timothy.pardee@rafaelpharma.com